Document jyaeBOQ5aZ0dok9Q9GerdbOY5

-C?P w' - 5L;2 a c M o T3 0) 2 fT5 U tn ro c M U-( O 05 C 3 C A 01 -U O rM ^0 5m 0> CD fH 4) O cn c O -h -U > cn 0 0) 5m 1 cu CO < 0) *a '0 aJ ca fd C u a 4-> to 0) 4) 3 -C P 31 0 U1 4) S rM 4) 03 A V4 4J D rV-4 *rCM 04 MM 0 U-i Cl, H X aa 'O c 05 w cp CP f--Vi cn < u u V c CP TJ 0j c 3: <3 0 CJ 03 S <H >. A CU PLAINTIFF'S EXHIBIT Bril. J. industr. Med., I960, 17, 260. DIFFUSE PLEURAL MESOTHELIOMA AND ASBESTOS EXPOSURE IN THE NORTH WESTERN CAPE PROVINCE BY J. C. WAGNER, C. A. SLEGGS, and PAUL MARCHAND From the Pathology Division, Pneumoconiosis Research Un<t of the Council far Scientific and Industrial Research, Johannesburg, West End Hospital, Kimberley, and the Department of Thoracic Surgery, University of the Witwatersmnd and Johannesburg General Hospital (RFCEIVEO tor PUBLICATION APRIL 24, 19GO) Primary malignant tumours of the pleura are uncommon. Thirty-three cases (22 males. II females, ages 31 to 68) of diffuse pleural mesothelioma are described; all but one have j probable exposure to crocidolite asbestos (Cape blue). In a majority this exposure was in the Asbestos Hills which he to the west of Kimbe in the north west of Cape Province. The tum.uir is rarely seen elsewhere in South Africa. Mesothelioma cf the pleura is regarded as an sin co mmon tumour. In the last four years c have seen 33 histologic::.! proven cases; 2S cf these had some association with the Cape asbestos field and four cases had been exposed to asbestos in industry. The tumour is rarciy encoumeied elsewhere in South Africa. During the past five years, with the exception of the present series, no neoplasm of this nature has been diagnosed amongst 10.000 lungs examined at the Pneumoconiosis Bureau in Johannesburg, or in the Pathology Department of the South African Institute for Medical Research. Higginson and Oetlle (1957) did not observe a single case in their survey of malignant tumours occurring in the Bantu and Cape Coloured population of Johannesburg and the North Eastern Transvaal. Our first necropsy specimen of pleural meso thelioma with asbestosis was examined at the Pneumoconiosis Research Unit in February, 1956 (Case 1). During the early months of that year, one of us (C.A.S.) in the Northern Cape, treated six patients with gross pleural thickening. Pleural biopsies from two of them showed the features of mesothelioma. In the ensuing two years, eight further cases were found from this region and five from elsewhere in the Union. During this period C.A.S. had become perturbed at the number of these unusual tumours occurring amongst his patients, and stimulated an investigation. At this stage there were two reasons to suggest that asbestos might be implicated. First, ashedos was found in the lungs of the first case (Case 1). and venn!'-. i0 of the c^scs CaiTJw from z t*,? -n suspected cases of tuberculosis were referred . large asbestos mining area. This hypothesis - not be supported at once from the or-emui 'u-ii-.t* obtained from the patients, for they io.e ucee i..,, wives, domestic servants, cattle heruciv. laimo'. j water bailiiT, an insurance agent, and an account-e t. none of whom were yvorking on the asbestos inu.c at the time. V/e therefore undertook a dct.n'ec irvevtigation of their past occupation and pU-e ' residence, and the association with asbestos r.- posure was discovered. The cases are sinnnurircJ in Table 3. Previous biopsy specimens v.eic u examined, and new cases diagnosed. ir..!..2.--.. asbestos miners. In only one case do the rcl.:t ei deny that the patient either visited the tube.:, v mines or was exposed to asbestos. This is a preliminary publication and the pm!''.-;-: is being intensively investigated. The Asbestos Area cf the North-Wevt Cape According to Hall (1930) asbestos v.so discovew-.t by Lichenstein near Prieska during hi', travels tween 1S03 and IS06. Since then < has N-en established that the asbestos deposit.; '\tend 20 miles south of Prieska, northwards ihrinirh t western part of the magisterial dixtrf:> 1,1 ] the eastern portion of the magister. I Postmasburg and finally, to the wester.'1 `' I } DIFFUSE PLEURAL MESOTHELIOMA 261 ! -a the our .-condly. o which J from a :s could historic* d hou.serinert, a ountunt. os mines detailed place of stos e\miri/cd were rc-.cludirv.: relatives asbestos problem Cape iseoverrJ avelv hehas Nrrr :nd from ough the f Hay. t<> 'istrict of :ca of the district of K'.uruman (Fig. 1). These deposits occur in the slopes of a range of hills covering an area of approximately 8,000 square miles. Known as the "Asbestos .Mountains-', these hills extend more or less bngitiadinally between 22-303 and 23 E. The whole area, is semi-arid, sparsely populated, and, apart from mining, cattle ranching is the only important occupation. In the Kuruman area several large tracts of land in or abutting on these mountains have been reserved for the aboriginal inhabitants and here whites may only reside in the immediate vicinity of the mines. The type of asbestos mined throughout this area is crocidaZ\te, better known as Cape Blue Asbestos. The chemical analysis of the fibre is given in Table 1. Crocidolice is the fibrous form of riebcckitc and all stages of Eransformation from a massive riebcckitc rock through lamellar riebeckite to asbestiform crocidolitc occur in this region. Magnetite is frequently associated with the crocidolitc (Vcrmaas, 1952). Mining of asbestos first began in the Prieska district in 1893 and gradually spread northwards. In 1908 production had begun in the Kuruman dis trict. Between 1916 and 1918 a large number of claims were taken up. This northward trend has continued and in about 1950 mining started at Pomfret near the Bcchuanaland border (Table 2). Initially the ore was quarried in numerous small open cast workings. This was followed gradually Table 1 CHEMICAL ANALYSES OF CROCIDOUTE AND AMOS1TE (from Vermoat, 1952;. s,o, A.1,0, Fe,0, FeO MgO CaO Nl,0 K,0 >1,0H.Ot- TiO, MnO F Crocidolit* 5o! 9:o4 18 64 19 39 1 }7 0 19 6-07 004 02__--_331S ---- Araosite 409 6437 334-1633 6-57 0 52 0 02 0 20 02-3017 0-25 061 001 Total 100 73 100 4S I 262 BRITISH JOURNAL OF INDUSTRIAL MEDICINE Table 2 POPULATION OF THE MAGISTERIAL DISTRICTS IN WHICH THF. ASBESTOS FIELDS ARE SITUATED (taken from Union Census 1021, and 1951) District Pneska Kuruman Poscrrusburg Population 192 Whites | Non** hues Total 3.4)0 4.71) 4,499 1 4,tT9 1 8.J09 16.698 21.411 8.814 i IJ.3I3 Included in (he Ha> District Whites 3.361 4.818 2,757 4.887 Population 1951 No-*hltM 10 847 2J.779 9.6)1 21.019 Total 14.204 28.397 I2.3S8 25,904 by a type of shallow mining; inclined shafting be today the non-white prefers to live as close as came more common after 1930. possible, and the children play on the dumps from According to Frood (1915), the quarrying was a the mine and milt. family affair undertaken by the local inhabitants. The men quarried the rock, which was sorted and then hand cobbed by the women and children. Hand cobbing consists of separating the fibre from the banded ironstone by striking the rock cob with a small hammer, .-is the market was selective, a Case Histories The following eight case histories illustrate various aspects of the disease and the different types of exposure to asbestos dust. rotary sieve was sometimes used to grade the fibre Case I.--B.P., a Bantu male, 36 years of age (born and eliminate the small particles of dust. After 1920), was a mine labourer, and was the first case grading, it was bagged and weighed. The asbestos was then transported by donkey wagon to the nearest rail-head. Before the establishment of the railway in this area between 1923 and 1930, such a journey couid :us: as long as 10 days. This transport was cer.er..!! ' ur.ienaj.cn by *rate youths (farmers' sons) unde: contra;:. Trie white inhabitants played very little par. in actual recovery of the fibre, being nearly diagnosed as a mesothelioma with evidence of asbestosis. He was born in the Kuruman dislrict but it is not known whether he worked in the asbestos mines. He was employed on the Wituatersrand gold-mines underground for two years and in the change rooms for a further 11 years. A radiograph taken a: a mine hospital on August IS. 1955 showed a massive right-sided pleural eiiusiun, and 3,000 ml. of fluid was withdrawn. Ho was ailnutted always employed in the role of managers or over seers, issuing stores and supers isin;ithe grading and weighing of the fibres. Farming activities were and are still carried cut round the mines. Since the 1939-1945 war, the demand forcrociuolite has enormously increased. The lucrative claims have been bought by registered companies, others have been abandoned. As deeper arid richer deposits have been found, vertical shafts are being to the VV ltwatersrand Native Labour Association Hospital on August 24, 1955. and two days later aspira tion yielded 1,000 ml. ol thick gelatinous pus "which could be pulled out in threads'". He was treated with frequent aspirations and instillation of varidase but without improvement, and heuclied on February 15, 1956 (Martmy, 1956). At autoosy the right thoracic cavity was occupied by a large gelatinous tumour which displaced the mediasti num and compressed the left lung. The tumour had sunk. However, the mines with large shallow deposits are still using the inclined shaft and tunnel, and quarrying is stilt used by the few remaining smaller producers. With the building of more nulls, hand cobbing has diminished. In 1915 the first crushing mill was established at Kocgas in the south. This was followed by a large mill at Kuruman infiltrated the pericardium. The right lung was com pletely compressed by neoplastic tissue (Fig. 2) but the right bronchial tree did not show any eviJcnce of a primary bronchogenic carcinoma. Histological sections of the pleural growth showed a papillary mesothelioma (Fig. 3). There was evidence of asbestosis in both lungs (Fig. A). (operated between 1926 and 1931) where it was Case 4.--K. H., a white female, 56 years of age (born situated within 300 yards of the main street, close to which cobbing was also done for a few years (1927-1930). This was followed by a mill at Priesha in 1930, which was completely rebuilt in 1957. Griquatown had a small mill in 192S. The practice today is for one mill to serve several mines in the immediate vicinity. In the early days the manager and labourers lived IS9S), was a social worker, who could only have had a short exposure to asbestos as a child and probably a further slight exposure as a young woman. She may have paid several short visits to the mines with her husband at a later period. She was born in Griquatown where she lived until she was 5 years of age. Her family then moved to Kimbeifey where from 19(0 to 1922 she worked as a clerk in an asbestos warehouse. Her husband owned an within a few yards of their place of work, and even asbestos nunc from 1933-1940. <`.t , "A * osc as - front various vposurc c (bom "*l case tvstosis. : known He W3S rground further :;ust IS, cflusion, : Jmuted .ociation r aspita. "which ted with 'esc but uary 15, t'-pie J by mediastiaour had >as com.) but the -ec of a I sections jthehonta in both age(born ace had a robably a She may with her unlit movcJ to ked as a o.srcJ an VCi; I I ( \ I II Vj." SKA. DIFFUSE PLEURAL MESOTHELIOMA ^ ` h - si. 263 ' -- -* ' r- ;*. c? 'i. 1 ^-*4.. -*% . ; * n . : -V . a-- e; *.. - 'V" ^ ^ *v^ - V r f/.-'Tl-.X .1 * r- -g? . r F\ ~ >iS=-&r V' * M cu , .w-.Jid -. k><L *, , " * g .' <? a . -* > ^ ' *r >r; .*ft eOar> | V? " A .vvJ Vv>`? >"' ' ^ l*s' J3 - _' w *_ Xi ?9 St * w^ 1 % r- ^ _` erf/ . ^^ Zl'' : ,. < la*. -h'* t Fig. 2 I Fic. 2.--High* lung of Case I showing a tumour compressing the lung substir.ee. I Fig. 3 --CelluUr sUuciur* of tumour of Caj< !. < 40 Haemaiosslm inti eostn. FtG. 4 --Sections of lung from Cose 1 showing asbestos bodies, x 40 Hiemaio^Un and costn. O Ftf > a. ' \.t ^ - v%,` a?'? .v * ` S'itrts. v. . . 1 '. * * . \ T' ^ , 1 (yCO c^sNo - ^ ^ ; X ~r O se s. / [ ( i, i tin cn i i .j 264 BRITISH JOURNAL OF INDUSTRIAL MEDICINE Fic. 5.--On July 21, 1954. ' O' Fig. 6.--On July T, 1955. CO CD ' i i t > i Ftc. 7.--On March 3. 1956 Fig. 8.--On Jul> 3, 1956 Fo. 5, ^ 7, *rJ ? Radiograph* shoviin; d>lopm<rnt of turnout in Osc 4. I DIFFUSE PLEURAL MESOTHELIOMA 265 V .^ She was referred to the West End Hospital, Kimberley, on July 19, 1954, because of dyspnoea and right chest discomfort of acute onset. The chest radiograph showed a loculated pleural effusion at the right base. Straw-coloured fluid was aspirated, which on examina tion was found to be negative for .If. tuberculosis but contained mesothehil cells arranged in acini. At thoracoscopy in Johannesburg on August II, 1954 tumour nodules were seen on the parietal pleura. Histo logical examination of the b.opsy specimen showed a mesothelioma. Deep therapy and radio-active gold instillation in September, 1955 caused initial regression of both the pleural fluid and nodules but did not arrest the progress of the disease. She received a further course of x-ray therapy without improvement and died in January, 1957. The liver was enlarged and nodular before death but no necropsy was done. (Tigs. 5, 6, 7, and 8 show the radiological development of the tumour in this case.) Cast 14.--SS.. a Bantii male, 40 years oT age (born 191S), was an asbestos m.rer He was bn"n in the Kurumun district and as a child often played on the asbestos dump near an asbestos nunc lie suh.-e-iuently worked with ashestos for several y.ar>, bemg employe.! at an esVsto. r.vnc v ;g hb:c f-o , 19't 41 In 1947 he worked oh a V.htwat.r-a.-..! gol.i i..ibut returned to the Kurumun district in 1943 where he worked as a farm labourer until his front illness. He was admitted to the West End Hospital on March 3, 1959. He had been well until July, I95S when he became aware of pains in tiic right side of his chest. In addition he had a slightly productive cough and short ness of breath on exertion. Chest radiograph on March 9, 1959 showed obliteration of the right lung field. Asbestos bodies were found in the sputum. Needle biopsy showej histological features consistent with a mesothelioma. Aliro?sv.--The right chest v.ns occupied by a huge whitish tumour which infiltrated the mediastinum, extending through the diaphragm onto the superior surface of the liver. A straw-coloured effusion was present in the left pleural sac but the left lung was not affected. The mediastinal, cervical, and paraaortic abdominal lymph glands to the level of the renal arteries were infiltrated with tumour. fn the right lung it was found that the tumour mass had infiltrated along the interlobar fissures. Thu lobes of the lung were compressed into three small segments (Tig. 9). On h'stoh'gv.il section a papillary type of plc.i'u! rr.-moth viam i was seen (Tig. 10) which had ir'ikfitcd into the lung jv.n-neh.vnia in some areas. There s.e, marked f.nphatic spread throughout the / 266 BRITISH JOURNAL OF INDUSTRIAL MEDICINE lung. substance. Numcrrous asbestos bodies were present in tr-c air spaces and occasional bodies and fibres were seen in the intcrstitio.u tissue. The lung itself was markedly atelectatic. Evidence of asbestosis was observed in the left Luang. Case 15.--S.S.V., is white female, 42 years of age (bom 1916), is a housewife, who lived on a mine near Johannesburg and was. treated for tuberculous pleurisy for sis months. It w.as only after the histological diagnosis of a mesothelioma had been made that her previous history was obtained. In addition, it was subsequently learnt than her father (Case 22) had been bom on the asbestos Bead and had along mining history. The patient was bom in the Griquatown district and weni to school at Kinzuman. She spent most of her youth in the asbestos belt. She has lived near Johannes burg for 20 years. Ln March, I95S this patient developed right chest pain and rapidly incieasing shortness of breath. She was admitted to hospital tund 2,500 ml. of slightly blood stained fluid was reicvxved from the right chest. A thoracoscopic examirrvfion was carried out on July 27, whesi a small biopsy was taken but this consisted of fibrous tissue. Bronvchoscopy was normal and no neoplastic cells were observed in the bronchial washings. ,W. :ubtrc:tbsts was red cultured from numerous speci mens cf sputa, pleura! duid nor from the bronchial stas-u:gs. Site was acc--atted to a Johannesburg nursing home on October 15. Iv5-S. Radiographs then showed massiie thickening of the right pleura with fluid ez the right chert. At thoracotomy (Mr. Dennis Fuller) me parietal plenra was 2 cm. thick, "hird as rock'' and stopped with great difficulty from the chest wall. The visceral peel stripped fairly easily from the upper lobe but separation became more difficult over the lower lobe where ti<e peel was thicker. During the decortication a nccracac mass was found in the paren chyma of the left lower lobe. At the base, confluent w ith the diaphragm and peefcaps the mediastinum, was a hard craggy mass which co*uid not be removed. Histological seesvons of the speciirven revealed an adenoid form of tubular mcsothcliomau Subsequent three specimens of sputum were examimed for asbestos bodies but none were found. The patient is still aJcvs (April, I960), but her condition is deteriorating. Case 22.--D.A.B., a. white male. 68 years of age, and a farmer, was the father vzf the pre\ ious patient. Although a diagnosis of pleucud mesothelioma was made in January, 1957 it was Knot until July, 1959 that details of his exposure to nsbestxns was obtained. He was born in Gri-fuatown and went to school there. He worked in Kurumn.cn, Postmasburg and Griquatown until the age of 62. Between I9IS and 1932 he worked as an asbestos miner underground and was mostly in charge of blasting. Between 1932 and 1944 he farmed in the district but rclurr.ed to asbestos mining from 1945 to 1952. In January, 1957 the patient consulted his doctor be cause of left-sided cU-st pain with cough and s'lght haemoptysis. He was referred to the Johannesburg General Hospital for investigation. The chest radio graph showed gross pleural thickening with a basal pleural effusion on the left side. He was admitted to hospital and on June 10, 1957 a thoracoscopic pleural biopsy was taken. This showed the features of a meso thelioma. On June 24, 1957 an attempt at decortication was made. The left upper lobe was stripped easily but the grossly thickened pleura was so adherent to the lower lobe that the attempt was abandoned. Sections of the pleura confirmed the diagnosis of mesothelioma. He died on December 13, 1957. Case 16.--A.N.V., a white male, 50 years of ace (bom 1906), was a farmer, who was born at Griquatown and went to a village school near an asbestos mine. From 1914-16 he transported asbestos in donkey waggons from Hay to Prieska. During these journeys he often slept on asbestos bags. In 1914 he worked in an asbestos mine for a month. The patient became ill in December, 1955 with vague substernal pain and dyspnoea. A left-sided pleural effusion was diagnosed and he was referred to Mr. 3. K. Brcmmcr in Pretoria. There was no evidence of malig nancy in bronchial and scalene biopsies. Some apical pleural thickening and a dense homogeneous opacity at the base of the left lung was seen in the radiograph on August 3. 1956. Thoracotomy (Mr. Brcmmer) in February, 1957 revealed a thickened nodular pleura with a large mass on the left diaphragm. A mesothelioma was seen on histological section. In April, 1959 he was examined by Mr. J. D. Visscr in Kimberley who found small nodules in the subcutaneous tissue over the neck and chest. A large firm mass was found in the thoracotomy wound and a mass was present in the left hypochondrium. There was generalized lymphadenopathy and numerous nodules were present on the tongue. Chest radiographs showed the left pleur.il cavity to be obliterated. He was one of the few cases to develop widespread metastases. A biopsy of one of the subcutaneous chest nodules showed a similar appearance to those seen in the original specimen from the pleura. The patient died on May 22, 1959. No necropsy was performed. Case 24.--D.G., a white male, 32 years of age (born 1922), by profession an accountant, was born in England but came to South Africa as an infant. He spent his early childhood in Kurumau and left at the age of 7. He later qualified as a chartered accountant in Kimberley. In 1944, at the age of 22, he had been discharged medically unfit from the army because of a left pleural effusion. Neither then nor on many subsequent occasions were acid-fast bacilli found, either in sputum or pleural fluid. His only subsequent contact with asbestos was the auditing of the books of an amosite mine in the Transvaal. In September, 1953 he complained of left-sided chest pains and shortness of breath. A radiograph of the chest showed flattening of the diaphragm on the left side v .tfi obliteration of the costoplircnic angle and thickening of the oblique fissure. He was seen on numerous occasions e Johannesburg "he chest radio% w-ith a basal a as admitted to coscopic pleural tures of a mesoai decortication ipped easily but adherent to the -id. Sections of f mesothelioma. tars of age (born Grkjuatown and os mine. From -y waggons from he often slept on .n asbestos mine 1955 with vague .ft-sided pleural red to Mr. J. K. ider.ee of malig:s. Some apical e radiograph or. . Bremmer) in nodular pleura A mesothelioma r. J. D. Visser in He subcutaneous ,a firm mass was mass was present was generalized ,'es were present _-d the left pleural ' the few cases to .'S chest nodules ,-n in the original died on May 22, ars of age (born bom in England t. He spent his the age of 7. He nt in Kimberley, hanged medically pleural effusion. : occasions were or pleural fluid, ibestos was the e mine in the f left-sided chest -.iph of the cl On: :'\c left side a nh r.J thie'sening of .erojs o-:ca".'i,s I l i I I 1 I fr' DIFFUSE PLEURAL MESOTHELIOMA 267 - -- - TV V ft -*r I I Fic. M.--On September It, 1956. Fig. 12.--Oft August 2J. 1957. F<gs. 11 anil "72, -- Radiographs shoeing development of tumour in Case 24. from 1953 to 1957. A radiograph taken early in 1956 showed the development of a left superior mediastinal shadow which enlarged progressively (Fig. 11) and later the cfe elopment of diffuse nodular pleural thickening on the left During 1957 similar but less marked changes deveJapcd on the right side (Fig. 12). He consented to biopsy in June, 1957, and, at operation, a diffuse pleural malignancy was present. Sections of the parietal pleura only were removed and the h-rstological appearances were those of a meso thelioma. He died on October 6, 1957. A necropsy was not performed. Case 30.--C.F., a white male. 50 years of age (born 1909>. is a storekeeper, with a history of industrial exposure. He has never been near the Cape Asbestos Fields. He was bom in South West Africa and lived there until the age of 21. From the age of 21 to 26 he worked in a factory in the Cape as a boiler-maker and fitter. He volunteered the information that he had worked con tinuously with asbestos, lagging pipes and boilers. He remarked that the remor a I of asbestos lagging from old pipe-, created a scry dusty atmosphere and that lie v.calJ coucrr a lot at such work. Between 26 anj 32 years of age fv: worked in a History in Johannesburg in a similar capi.c.t) but was not evposcd to such he.isy du-t con cern.-..:! in> lor the pnO 20 years He Had not been in contact with jsbehn.p.nncs vcic na.de fron fact in the Cape as ter the natinc of lit. t.'j-s.11>> .J 1 and these have revealed that during the relevant periods Cape crocidolite was exclusively in use. He was first seen on March 74, 1959 complaining of cough, pain in the right chest and recent onset of breath lessness. Three pints of fluid had been aspirated from the pleura and cytologieal examination showed the presence of malignant cells. The radiograph showed marked pleural thickening and hydro-pneumothorax. On March 17, 1959, a thoracoscopy was done. The pleura felt thickened and the lung was collapsed and immobile. Several biopsies were taken. These showed the presence of a mesothelioma. The underlying lung showed the presence of asbestosis. He was treated with nitrogen mustard imra-pleurally and his condition temporarily improved. When last examined he com plained of increased breathlessness. Discussion In 1924 Robertson denied the existence of primary' malignant tumours of the pleura and con sidered diem to bo secondary in origin. Since then, on the one hand, Willis (194S, 1953) and Smart and Hinson (1957) have supported Robertson's views, while on the other hand, primary neoplasms of this nature have been described by many authors in recent years. These include Tobiassen (1955) in Sv.vd.cn, Bclloui and Bovo (1957) in Italy. Godwin (1957) m the United States, and McCa.ighe,, (I95S) i i T0 SLL LSI 268 BRITISH JOURNAL OF INDUSTRIAL MEDICINE in Britain. Evidence in support of the mesothelial origin of these tumours can be found in the tissue culture experiments of Stout and Murray (1942) and Sano, Weiss, and Gault (1950). The variegated histological pattern of tumours arising from the mesotheliutn of the pleura was remarked on by Klemperer and Rabin 11931). Such a variation is appreciated when the mulupotentiality of the cells lining coelomic cavities are considered. Maximow first demonstrated this feature in 1927. Novak (1931) stated that the mucosa of all parts of the Miillerian canal and the germinal epithelium were derived from these cells. Keasbcy (1947) showed that in the embryo, the mesonephros, metar.ephros. Wolffian body, genual ridge, and all dependent urogenital structures arc derived from the mesothe'ium. Campbell (1950) considered the presence of both epithelial and mesenchymal elements a major diagnostic feature. In describing the histology of 11 of these tumours McCaughcy (I9JS) demonstrated that cither the epithelial or the mesenchymal element might preJcmir.ait. He classified his cases into the f.rilcwmc feur groups: Tumours of epithelial character, rumours of mesenchymal roe: tumours cf mixed type, and tumours of anaplastic type. Using McCaughey's classification on our series of lancers, the majority arc. as in Campbell's series, of the mixed type. Of the remainder, a few showed the papillary tubular structure of the "tumours of epithelial character", and there were several of the anaplastic type. One case had the appearances of a "tumour of mesenchymal type" but even in this case primitive tubular structures weie seen. Apart from the original case all the histological diagnoses were made on biopsy material. Three of these biopsy findings were confirmed at necropsy. In the remainder, we have had to rely on clinical and radiological examination to exclude other primary sites of malignancy. Following the work of Meyer and Chaffee (1939, 1940), the possibility of demonstrating hyaluronic acid in these tumours both chemically and histochemically has been considered as a diagnostic aid. Both these ioxestigations are still in an early stage (Ilarington, 1959). Preliminary results of the histochemica! experi ments show that there is meiachrotr.aiic substance in both the stroma and glandular structures of the tumours. This metachronusia car. be reversed by incubation with testicular hyal muradase. This material stairs strongly with Hale s 11946) colloidal iron method. The periodic acid Snuff technique has given variable reactions. These results are not xpeeiiri; fo: hye.V.-omc acid tri. are strongly suggestive it.-> pic.-.nce. The amount of nictachromatic substance in these tumours has varied considerably. This wc think is partly due to the fact that until recently wc had not appreciated the solubility of hyaluronic acid in aqueous media and the majority of these tumours were fixed in 10% formol-saline. Further, Lison (1953) states that the mctachromasia of hyaluronic acid is optimal at a concentration of 1/10,000 and gradually decreases at higher levels. When the high concentrations that Meyer and Chaffee (1939. 1940) found in their tumours are considered, this variation in metachromatic properties seems to have been partially explained. In addition, with the great differences in the histology of the various lesions, it would be logical to expect certain tumours with a marked adenoid appearance to secrete more than those with an essentially non-glandular structure. Three of the five autopsies performed showed evidence of peritoneal metastases. In the other two, intra-thoracic spread was observed, in one case to the other lung and chest wall, and in the second to the mediastinal lymph glands and pericardium. Biopsy evidence of metastases has been obtained in .wo cases, one from the omentum arid the other front the subcutaneous tissue of the chest wall: whiie a third patient developed an implantation nodule in ::;c thoracotomy scar which showed a similar appearance to that of the previous biopsy specimen. The first recorded case of carcinoma of the iung associated with asbestos was described by Lynch and Smith (1935). By 1955. according to Doll, a total of 61 cases Ijad been reported. Included in these cases was one mesothelioma. Cartier (1952) mentioned two cases of diffuse mesorhclioim from a Canadian chrysotilc mine. A further three cases were described by van der School (1958). Un fortunately no indication is given in the literature regarding the type of asbestos to which the majority of recorded cases of carcinoma were exposed. However, discussion with management and medical officers of two of the factories, in which the majority of the cases reported in Britain were employed, suggests that most of these workers were handling chrysotile asbestos (Wagner, I95S). The possibility that some of these people may also have been exposed to crocidolite dust cannot be excluded. Attempts to produce tumours in experimental animals by exposing them to asbestos dust have been made. Vorwald and Karr (1938) were unsuccessful Lynch, Mclvcr, and Cain (1957) succeeded in pro ducing tumours in mice, but lung neoplasms in hi: control animals were far too numerous for th. results to be considered significant. On the o:h. hand Schnuhl (195S) working in Dru.ktey' laboratory has been able to produce sarcon.is : rats. This has occurred afiei subcutaneous w i tic substance in these aly. This we think is il recently we had not f hyaluronic 2cid in rity of these tumours line. Further, Lison omasia of hyaluronic ation or 1/10,090 and . evels. When the high d Chaffee (1939. 1940) isidered, this variation seems to have been ition, with the great the various lesions, it rrtain tumours with a to secrete more than glandular structure. es performed showed ises. In the other two, rved, in one case to the d in the second to the 1 pericardium. Biopsy been obtained in two and the other fiom the ,,~st wall; while a third nation nodule in the :d a similar appearance specimen. carcinoma of the lung s described by Lynch . according to Doll, a reported. Included in lioma. Cartier (1932) a mesothelioma from a A further three cases Schoot (1953). Un even in the literature s to which the majority noma were exposed, nagement and medical s, in which the majority ritain were employed, workers were handling 1953). The possibility may also have been cannot be excluded. nours in experimental asbestos dust have been 933) were unsuccessful. 95") succeeded in pro- ' lung neoplasms in ins uo ncmerous for the -ifico.ru. On the other tking in DrueV.r-e;. -s 1 produee s.r^-. . , fler subcutatv; us ..:,d j j i < ' I I j | I j j I j . | i 1 j ' j | j I ! , I j ' | j DIFFUSE PLEURAL MESOTHELIOMA 269 intrapcritoneal inoculation of both asbestos fibres (Table 3). Eighteen of these 25 cases were born in and dust. He states that "mineral asbestos" was the vicinity of the mines and two arrived in the used but does not name the variety. district as infants. Of these 18 people 11 admit In our series of mesotheliomata, histological definite childhood exposure to the dust and two evidence of asbestosis has been observed in eight others were exposed industrially in later life. In of the 10 cases in which lung parenchyma was in addition two patients with childhood exposure later cluded in the specimen examined. No lung tissue worked in the asbestos mines. Three cases arrived was present in the biopsies from the remaining in the region at an older age but were employed cither 23 cases. It was only in the four cases that came to on the mines or in transporting asbestos. A further necropsy that large sections of the lung tissue were three of these 25 cases have had industrial exposure, available for examination. In all of these specimens and in only one case do the relatives deny any evidence of asbestosis was found. exposure to asbestos dust. ^ At first it was thought that the presence of The four industrial cases arc significant. Two ' numerous asbestos bodies, fragments of fibre, and of the patients were lagging locomotive boilers and__, dust immediately below the pleural elastic laminae one was lagging steam pipes. A man, who was an in these specimens, might have been significant in upholsterer by trade, was a...ployed in making the pathogenesis of the tumours. However, it is fire-proof clothing from 1939-1945. As far as can more probable that this distribution is a result of the be ascertained these people were never in the CT marked atelectasis. Similar features have been Griqualand district. These findings tend to add CT> observed in atelectatic lungs of asbestos miners in support to asbestos being the common factor in the cn which no mesotheliomas have been observed. development of these tumours, and to counter the Pleural fibrosis has been a common finding in suggestion that there may be some other environ cases of asbestosis and in some cases large pleural mental cause in the region of Griqualand West. claques measur.r.c up to 1-0 cm in thickness have If asbesros dusr is a factor in the occurrence of been seen. These plaques, which were first described these cuinours. similar cases might have been cx by Gloyne (1933;. have been observed following pected from the neighbourhood of the Transvaal exposure to both amositc and croeidolite asbestos asbestos mines in the Petersburg and Lydenburg dusts. In these cases of benign pleural thickening districts, where croeidohlc and amositc asbe-:o is no evidence of stromal metachromasia has been mined. According to Vermaas (,1952). croeidolite observed. arid amosite occur in the same scams in the Peters In all the histological sections of pleura examined burg district. As can be seen from Table 1. amosite in the cases of these mesotheliomas and in more is similar in composition to croeidolite. In the past than 100 cases of asbestosis, no asbestos bodies, four years the lungs of 24 cases of asbestosis from fragments of fibres, or dust have been observed the Lydenburg district have been examined. In beyond the pleural elastic laminae. this material two cases of adeno-carcinoma have Three patients from the Kuruman district, with been observed. The one was in a white miner with clinical and radiological features consistent with 19 years' service, who had an adcno-carcinoma those of diffuse pleural mesothelioma had markedly arising from a bronchus. The other case was a abnormal cells in the pleural fluid. These cells Bantu miner who hud a peripheral tumour. No showed no specific features to distinguish them from service record was obtainable in this case. Only cells originating in secondary malignant pleural one case of asbestosis has been received from the deposits nor from the grossly atypical cells some Pictersburg area. All of these men were actually times seen in non-malignant pleural effusions. As employed on the mines at the time of death, the no biopsy or autopsy examinations were obtained in majority having had a relatively short service. Our these cases they have been excluded from the scries. findings suggest that mesothelioma occurs 20 to 40 The pathological evidence for associating these years or more after exposure to dust. Until com tumours with asbestos exposure is not conclusive. paratively recently the mining in the Transvaal As previously stated, only in eight of the 33 cases has has been on a small scale, and there were no settle evidence of asbestos been demonstrated. Of these, ments in the vicinity of the mines. six had a definite mining history and one had been The lungs of 20 asbestos miners from the Cape exposcJ to asbestos while lagging steam pipes. The Asbestos Field have been examined, in whom no other case was born in. the Kuruman district and mesothelioma was observed. One autopsy specimen nothing else is known of him, until his arrival at a consisting of three fragments of lung showed WitwatcrsranJ gold-mine at the age of 23. In the asbestosis and an adeno-careinoma. Radiological remaining 25 cases v.e can only present circum features of asbestosis have been observed in many stantial evidence of exposure to nibroos dust miners fiom this region, without anv suggestion of S-Q566653 - rwv '* , i 270 BRITISH JOURNAL OF INDUSTRIAL MEDICINE Table 3 DIFFUSE PLEURAL MESOTHELIOMA: ASSOCIATION WITH ASBESTOS (1) Gisc No. <D Year of Birth 1j ! m Ase | (4> Race Diagnosis 1 ! (3) i <*> : Born oo Sea Atbesim ' Fields l i (7) Asbestos Exposure <) Diagnosed on Biopsy c Necropsy 1<I0) cl,l> 1 aurvivi. Histological Evidence of Asbeatosia jSymptr^. }<in momii 1 1920 36 i M + ( Other history unknown until came to the Wit* 1 waters/and at the age of 23 -F F i 2 1913 42 ;mxd M +- Mined asbestos from 1930-3); left area at the 3 1902 53 i * F 1 4 1896 1W F age of 27 - r Lived whole life in a location near an asbestos mill F -4- Lived on asbestos Reids until the age of 3; +. -- -- - 29 It . 5 1923 ! 31 ' B M -j- worked in asbestos warehouse 1916-20 Spent all his workir; lire in the vicinity of mint* -- _ 6 1 1903 S3 : W F + Lived all her life in the *. tcmtcy of mires 7 < 1920 36 W M r Lived all his life m the vicinityof mines; worked ---- F -- -- Wi n J3 ! as a miner -- t- 24 8 1894 63 MXD F h From the age of 24 lt\?d in a village serving local 1 ii mines; often visited mines; watched cobbing f outside houses 4- 1 9 1905 32 J MXD M -i. Whole life spent near mines, digging wells -f. -- 10 1909 49 WM -U Lived at the mine from age 7-17 years; played -- -- 3, 3| !i on dumps and in mine as a boy: returned to I 1 assist from age 21-23 *-1 -- n 1896 | 60 MXD M T Whole life spent near mines; miner J9JI-33 fF 12 1910 > 4S 8 M -- Lived near mtr.es until the age of 17; miner 1927 j + j -- 13 1909 . 30 WF Lived near mine until the age of 21; played with i nj 12 . Still at.'r 1 i 14 1918 40 i1 BM fibre as a chilJ j +|-- Whole life spent near mines; miner 1938-41; ; 1 played on dumps as a child j O- 1 F -- 4- 7, 1 91 13 1916 42 W F -y ' Daughter of Cave 22: lived at mine until age of | i 20; went to school near cobbing sheds i 1-- -- Still alt*-- 16 1896 i 60 w M Went to schoof near mines; transported asbestos > 1 1914-16 1-- -- o 42 i 17 1911 Jj MXD F -- Lived on mipr wagon route till age of 15; J i 18 1920 :s a M ' several subsequent visas , -1 - Whole hie m the vjcmitv of the mine*; miner --3 i !94.<s 19 19:: J7 MXD V - Family lived at mine; rruner -- - 22 -- --. -- Still lv" 20 1906 53 w F -- Spent whole life m village on wagon route to , Kimberley --( -- -- 1 21 1912 44 w M - Lived in (he vicinity of mines until the age of 16; often on dump' as a child -- -- -- 16 22 1339 68 w M 'fchole life m tne vicinity ot the mines; miner i 1913.32. and l^:-?: - -- -- i: I! 23 1893 63 w F 1 -- Lived m the vicinity ot the mines until the age , of J0 1 -1 -- ! *, i 24 1922 ' 35 w M ! -- i Lived in the vicinity of a milt from the age of 1-7; ' J 1 played on the dumps as a child i -r } -- [ -- 46 1 11 23 1699 j 30 w F | -- Lived in a mining area trom the age of (0 to 18 1 years; after 1918 spent whole life in same town as Case 24 4W 9- 1 -- l -- i Still af.* 26 1893 49 w M - Mined and transported asbestos from 1929-33 l ; as overseer -- 1 --- -- l> 27 1904 52 w W . _ ' Bom in North West Cape; transported asbestos j from 1920-24 -r | -- 0 15 28 1699 60 w M - Lived whole li: on farm in mining area from i 1 j the age of 12: transported asbestov 1916-21 --! -- 29 191) ! 44 w .M -- Maintaining locomotive boilers 1931-45 , -r 1 -- -- 1 Still at 1i 30 1909 30 i1 31 1913 44 w Ms 1 Maintaining steam pipes in explosive factories w M1 0 1 1930-40 I Worked as fi;:er on railways* maintaining i -r 1 -- + 1 Stilt it.-:, !t i locomotive boilers, dates unknown I 4* > -- -- j6 _i i 1I a i 1903 i 49 W' M Making asbestos blankets for the Air Force i 1t 1939-45 1 ~ -- 3J 1 2890 | 39 wF - No history of exposure to asbestos I4|-- l 7 -1 i KYb: Column 4-- Ra.e- W While Column 6 -- Born on asbestos f.elds Cotumn 9-- -r " Necropsy done Cotumn 10 4- -- Positivchistolog.calcvuJtft-'. MXD Mixed (Coloured) -- ~ Not bom on asbestos -- * Necropsy noc done of asbevtosi* ' i B - Bantu Reids 0 * Unknown * Only j.tiall frjjmcuts of parietal pleura submitted at -- mi lung tissue submitted 0 Small fragments of tur*. autopsy for histological tissue, but no c> iJence examination asbc&tosis I ! tumour formation. However, pleural involvement has been a common finding in. these cases (Hurw itz, 1959;. It is possible that there has not been a sufficient lapse of time after exposure for tumour dcsclopmen! in these cases. Further, the factor of individual susceptibility must also be con sidered. Wc svisli to record the great assistance that sc have rccoiied in this investigation from the medical prac titioners of the Griqualutid West District and the (10) J (W. , { Survj*j s'.otogk&l froro 1 :UeCe Of IfKtui sixuaii* SyMrtO-J (;.-t motvjy- j + 1! - ; 29 - 11 _ 30 _ 11 - ,J i 41 _ - 51 13 1 -- 12 1 + Still - 7| 9j - - StiJI al.vri 0 42 3 _ 22 * Suliji.-i- ! 16 1 1.. | - *I - 48 * 1I - SulU!.' . - ! 0 15 i SMI a' ' - 7J - Still 61 - 7I - 11 .ti -ehujotojicjl c^iwe"** fs l !j.*V ;.uc v>bm/.ie'i ill f*4 Ot' ba; r<" e-.uicncf c be coa- -nl v,j have .alien! prac.t and the D1FFUSE PLEURAL MESOTHELIOMA 271 thoracic surgeons and pathologists in Johannesburg, Pretoria, and Durban. We thank the Secretary of Health for permission to publish this paper. References BsHoni. G.. and Bovo. G (1957). Acte med. patar., 17, 367. Campbell. W. N. (1950). Amer. J. Path., 26. 473. Cartier. P. (1952). Arch. mduttr. Hyg5, 262. (Contribution to chi discussion > Dell. R. (19551. Brit. J. xnduue. Med. 12. St. Frood, G. E. B. (1915). Sfrmorundum on the Asbestos Industry in the Cepe Province. Report of the Government Mining Engineer, Unton of So'jih Africa, pp. 76-S2. Gloyne, S. R. Tubercle (Lond.), 14, 493. Godwin. M C ((957) Cancer (Pnt(ad), 10.298. Hut, C W .Sc.-.-r {Lond), 157, S02 Hall. A. L. (1930). .46*'<.*o in the Union of South Africa. Memo* randu/n no 12. Geological Survey of South Africa. Haringtoi*. J S. 0959). Personal communication. Higginson, J., and Oeitle, A. G. (1957). Acta in. tnt. Carter., 1.1, 949. Hurwit?, M. (1959). Proceedings of International Conference of Expert* on Pneuntcxonious. Johannesburg. Feb. 1959. ChurchiM. London. (In the pre**.) Keasbev. L. E. (1947), Amer. J. Path.. 13. 871. Klemperer. P . and Rabin. C. B. (I9JI). Arch. Path. {Chicago), It. 3a5 Liaon, L. (1953). Hwochimie el Cytoehintir Animates. pp. 332-337. Gauthier-Vlllars. Paris. Lynch. K. M.. and South. W A. (1935). Amer. J. Cancer. 24. 56. -------, Mclver, F A., and Cam, J. R. (1957). A.St.A. Arch, imduur. HUH, IS. 207. Martin). O. (1950). Proc. Teanxv. Sfine med. Offrs' Ais^ 33. 63. Miumow, A. (1927). Arch, exp. Zeli;>>rsch.. 4, J. McCaughey. VV. T. (1958). J. Path. Sacr., 7. 317. Meyer, K... and Chaffee. E. (1939). Prvc. Soc, exp. Biot. 42, 797. -------,-------(1940). /. 6to/. Chem., 1J3. S3. Novak. E. (1931). Amee. J. Ob act. Gynce., 22, 826. Roberuon, H. E. (1924). J. Cancer Res.. S. 317. Sano, M. ., Weis*. El, and Gault, E. S. (1950). S. thorac. Sunr., 19. 783. Schmihl, D. (1958). Z. Krebsfumck^ 62. 361. Smart, J., and Hinson. K. F.W. (1957). Brit. /. Tubcre.. 51, 319. Stout, A. P-, and Murray, M. R. (1942). Arch. Path. (Chicago). 34, 951. Tobiaasan. G. (1935). Acta path, mienbiot. scand., Suppf. 105. p. 198. van der School, H. C. M. (1958). AW. T. Gctmesk, 102. 1124. Yermaas, F. H. S. (1952). Trans, rcol. See. S. Afr., 55. 199. Vorwald, A. J.. and Karr. J. W. (1933). Amer. J. Path., 14. 49. Wagner. J. C. (1958). Stcm-mandum or* Pneumoconiosis Research in Europe. Submitted to the C-S.I.R. Willta, R. A. (1948. 1st ed. and (953). Pathology of Tunroun. Butterworth, London. Addendum By the end of June I960, a total of 47 cases of mesothelioma had been identified. In 45 of these a possible association with exposure to crocidulitc has been established. In one case a mesothelioma of the peritoneum was present. THE JULY (1960) ISSUE The July (.I960) issue contains the'foilowijig papers:-- Decompression Sickness during Construction of the Dartford Tunnel. By F. Campbell Golding, P. GrilFiths, H. V. Hempleman, W. D. M. Paton, and D. N. Walder. A Comparison of the " High-altitude " and " High-pressure " Syndromes of Decompression Sickness. By M. de G. Gribble. Phosgene Poisoning Caused by the Use of Chemical Paint Removers Containing Methylene Chloride in Ill-ventilated Rooms Heated by Kerosene Stoves. By W. B. Gcrritscn and C. H. Buschmann. A Study on the Acute Toxicity of the Tri-ary l Phosphates Used as Plasticizers. By H. F. Bondy, E. J. Field, A. N. Worden, and J. P. W. Hughes. Aerosol Inhalation of Ca.N'a2E.D.T.A. (Mosaiil) by Workers Constantly Exposed to Lead Poisoning. By Lj. Petrovic, Nl. Stankovic, M. Savicevic, and D. Poleti. A Biochemical Study of the Urinary Protein of Men Exposed to Metallic Mercury. By J. C. Smith and Agnes R. Wells. A Simplified Melliod for the Estimation of Nickel in Urine. By J. Gwynnc Morgan. Clinical, Bronchographic, Radiological, and Physiological Observations in Ten Cases of Asbestosis. By G. L. Lcathart. The Measurement of Occupational Mortality. F. D. K. Liddell. Observations on the Occupational Life History or the Coal Face Worker at Two Collieries. By O. P. Edmonds and D. S. Kerr. The Assessment of Llcctrocnccphalogruphic Changes and Memory Disturbances in Acute Intoxications with industrial Poisons. B_v B. C'hulupa, J. Synkova, and Nt. Scscik. Book Reviews. A number of copies arc still available and may be obtained from the Publishing Manager. British Mcihv.il Association. Tuvi'U'.k Square, W C.l. price Ps. 6t!. (i999Sui.$